Ancestral Mammal's Genome Reconstructed

It's not exactly Jurassic Park, but a team of researchers has reconstructed a portion of the genome of an ancient shrewlike creature believed to be the common ancestor of all placental mammals, including humans. The work may help scientists determine how changes in mammalian DNA over time forged the path for human evolution.

Tracing the evolutionary history of human beings requires some genetic knowledge of our direct ancestors. Until now, the best hope for obtaining this information was recovering DNA from well-preserved fossils. But because the DNA in fossils is often too degraded to work with, the resurrection of ancient genomes has enjoyed more success in popular fiction than in the laboratory. To get around this problem, computational biologist David Haussler of the University of California, Santa Cruz, and colleagues turned to computers instead of fossils. The team started with 19 modern placental mammals, including humans, pigs, and mice, and fed a 1.1-million-base-pair region shared by all of the animals into a computer program, the team reports in the December issue of Genome Research.

The program assumed that if a similar DNA sequence were present in a diverse set of the mammals, it must also have been present in the ancestor. For sequences that were different among the mammals, the program applied a complex set of criteria to determine which sequence most likely represented that of the ancestor. For example, the sequence of a species closer to the ancestor on the evolutionary tree, such as the lemur, was given preference over the sequence of a species farther down the tree, such as the hedgehog. An evolution simulator program that checked the likelihood of the living mammal sequences being derived from the ancestral sequence indicated that the team's final ancestral sequence was 98% accurate.

Haussler says that one of the most surprising findings was that, compared to the ancestral sequence, the rodent sequence contained two times more "new" DNA than the human sequence. This suggests that the lineage that led to humans underwent more dramatic changes than the rodent with fewer mutations. Haussler's team also found that some of the sequence of the noncoding--or "junk"--DNA in all species was conserved over time, adding further weight to the theory that this DNA is critical for survival.

"This is a really nice approach that gives us a rich source of information for studying human evolution," says Greg Wray, an evolutionary biologist at Duke University in Durham, North Carolina. He believes the approach will be adopted by many more scientists. "People will look back on this paper and say, 'This is where things really got going.' "